Ocena leukocytarnej ekspresji SIRT1 u kobiet ze zdiagnozowaną cukrzycą ciążową (GDM) w trzecim trymestrze ciąży

Background. Sirtuin 1 (SIRT1), a NAD+-dependent deacetylase, has been implicated as a key regulator of glucose/lipid metabolism, insulin secretion as well as adiponectin production and inflammation in metabolic disorders, including type 2 diabetes mellitus (T2DM). However, its role in gestational diabetes mellitus (GDM) remains widely unknown. Since GDM is associated with inflammation, the aim of this study was to determine whether leukocyte SIRT1 mRNA expression is alteredin GDM women in the third trimester of pregnancy, and whether this change is correlated with clinical characteristics of patients. Methods. Leukocytes were isolated from the blood of GDM (n = 135) and normal glucose tolerant (NGT;n = 52) pregnant women. After extracting RNA from leukocytes, a quantitative real-time polymerase chain reaction (qRT-PCR) approach was performed to assess SIRT1 gene expression in these cells. Univariate regression analyses were applied to investigate correlations between SIRT1 expression and clinic parameters of patients. Results. Leukocyte SIRT1 mRNA was increased 1.7-foldin the GDM vs. NGT subjects (p = 0.001) and it positively correlated with 2 h glucose concentration during oral glucose tolerance test (OGTT) in the whole studygroup and negatively correlated with pregnancy agein the GDM and NGT groups. The positive association was also observed between SIRT1 mRNA and plasma high density lipoprotein (HDL) cholesterol level in the NGT subjects. Conclusions. GDM is accompanied by leukocyte SIRT1 mRNA over expression associated with hyperglycemia. Additionally, there is a close and beneficial relationship between enhanced leukocyte SIRT1 expression and increased plasma HDL-cholesterol level during normal pregnancy.Wstęp. Sirtuina 1 (SIRT1) jest NAD+-zależną deacetylazą, która odgrywa istotną rolę w regulacji metabolizmu węglowodanów i lipidów, sekrecji insuliny, produkcji adiponektyny oraz stanu zapalnego w chorobach metabolicznych, w tym cukrzycy typu 2 (T2DM). Do tej pory brak jest informacji o związku leukocytarnej SIRT1 z cukrzycą ciążową (GDM). Zważywszy związek SIRT1 ze stanem zapalnym, celem badania było określenie zmian w poziomie ekspresji SIRT1 mRNA w leukocytach kobiet z GDM w trzecim trymestrze ciąży i skorelowanie ich z klinicznymi parametrami pacjentek. Materiały i metody. Leukocyty wyizolowano z krwi pobranej od kobiet ciężarnych z GDM (n = 135) oraz kobiet ciężarnych z prawidłową gospodarką węglowodanową (NGT; n = 52). Po ekstrakcji RNA z leukocytów poziom ekspresji SIRT1 mRNA w tych komórkach określono metodą ilościowego qRT-PCR. Korelacje między ekspresją SIRT1 a klinicznymi parametrami pacjentek analizowano z wykorzystaniem regresji jednokrotnych. Wyniki. Ekspresja SIRT1 była 1,7-krotnie wyższa w leukocytach kobiet z GDM niż w grupie kobiet z NGT (p = 0,001) i dodatnio korelowała ze stężeniem glukozy w 2. godzinie testu doustnego obciążenia glukozą (OGTT) w całej badanej populacji pacjentek oraz ujemnie korelowała z wiekiem ciąży kobiet zarówno w grupie GDM, jak i NGT (p < 0,05). Stwierdzono również istotną statystycznie dodatnią korelację międzyekspresją SIRT1 a stężeniem cholesterolu frakcji HDL w grupie NGT (p < 0,05). Wnioski. GDM towarzyszy podwyższona ekspresja SIRT1 w leukocytach, która jest związana z hiperglikemią. Ponadto zaobserwowano istnienie bliskiego i korzystnego związku między podwyższonymi poziomami ekspresji SIRT1 a cholesterolem frakcji HDLu kobiet z prawidłowym przebiegiem ciąży

The influence of anti-TNF therapy on CD31 and VEGF expression in colonic mucosa of Crohn’s disease patients in relation to mucosal healing

Introduction. Immune-mediated angiogenesis may play an important role in the pathogenesis of inflammatory lesions in Crohn’s disease (CD). The study aimed to assess the influence of anti-tumour necrosis factor (anti-TNF) therapy on the angiogenesis in relation to microscopic and endoscopic healing in CD patients. Material and methods. Colonic tissue samples from 17 CD patients were taken during colonoscopy before and after anti-TNF therapy. Endoscopic and microscopic severities were estimated using validated scores. Immunohistochemical expression of CD31 and vascular endothelial growth factor (VEGF) were assessed in parallel. Results. The expression of CD31 and VEGF decreased significantly after the anti-TNF therapy in parallel to endoscopic improvement; however, the microscopic activity did not change significantly. There was a correlation between the change in CD31 and VEGF expression (p = 0.01; r = 0.6), as well as endoscopic healing (p = 0.04; r = 0.4). CD31 immunoexpression correlated with the number of poly- and mononuclear cells in the infiltrates in the mucosal lamina propria before the therapy (p = 0.02; r = 0.5). Conclusions. We suggest that modulation of vascular proliferation can be a novel option to increase the efficacy of biological therapy in CD.

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements